Abstract

The ability of mammals to identify and distinguish among many thousands of different odorants suggests a combinatorial use of odorant receptors, with each receptor detecting multiple odorants and each odorant interacting with multiple receptors. Numerous receptors may be devoted to the sampling of particularly important regions of odor space. In this study, we explore the similarities and differences in the molecular receptive ranges of four mouse odorant receptors (MOR23-1, MOR31-4, MOR32-11 and MOR40-4), which have previously been identified as receptors for aliphatic carboxylic acids. Each receptor was expressed in Xenopus oocytes, along with Galpha(olf) and the cystic fibrosis transmembrane regulator to allow electrophysiological assay of receptor responses. We find that even though these receptors are relatively unrelated, there is extensive overlap among their receptive ranges. That is, these receptors sample a similar region of odor space. However, the receptive range of each receptor is unique. Thus, these receptors contribute to the depth of coverage of this small region of odor space. Such a group of receptors with overlapping, but distinct receptive ranges, may participate in making fine distinctions among complex mixtures of closely related odorant compounds.

An oocyte expressing MOR23-1, RTP1, Gαolf and CFTR is challenged with 15 sec applications of 35 ligands from our odorant panel (each at 100 μM). Each trace starts with an application of 100μM nonanoic acid, which serves as a normalization standard. All traces are from the same oocyte. Because the nonanol application occurred before the octanol response had ended, nonanol was retested at the end of the dicarboxylic acid screen (bottom trace). Scale bars: 0.5 μA, 10 min.

Oocytes expressing MOR23-1, RTP1, Gαolf and CFTR were screened with a panel of 41 saturated, aliphatic primary alcohols, aldehydes, monocarboxylic acids, bromocarboxylic acids and dicarboxylic acids, ranging in length from 4 to 12 carbons (15 sec applications of 100 μM, as in Fig. 2). Compounds yielding responses at 100 μM were also screened at 30 μM, 10 μM and 3 μM. Values are the mean of results from 4-8 oocytes (SEM values may be found in Table 1). Flat squares at the base of the graph indicate tested compounds or concentrations that did not yield a response. Blank areas at the base of the graph indicate compounds or concentrations that were not tested.

Oocytes expressing an MOR (MOR31-4 in panel A, MOR32-11 in panel B or MOR40-4 in panel C), Gαolf and CFTR were screened with a panel of 41 saturated, aliphatic primary alcohols, aldehydes, monocarboxylic acids, bromocarboxylic acids and dicarboxylic acids, ranging in length from 4 to 12 carbons (15 sec applications of 100 μM as in Fig. 2). Values are the mean of results from 4-16 oocytes (SEM values may be found in Table 1). Flat squares at the base of the graph indicate tested compounds or concentrations that did not yield a response. Blank areas at the base of the graph indicate compounds or concentrations that were not tested.